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BIOMARKER:

SOX2 overexpression

i
Other names: SOX2, SRY-Box 2, SRY (Sex Determining Region Y)-Box 2, Sex Determining Region Y-Box, SRY-Related HMG-Box Gene 2, Transcription Factor SOX-2, MCOPS3, ANOP3
Entrez ID:
Related biomarkers:
28d
Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors. (PubMed, J Exp Clin Cancer Res)
Altogether, our work highlights the importance of the HIF-1α-PLD2 axis for CSC generation and chemoresistance in OC and proposes an alternative treatment for patients with high PLD2 expression.
Journal
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NOTCH1 (Notch 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • SOX2 • SOX9 (SRY-Box Transcription Factor 9)
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SOX2 overexpression • SOX2 expression • SOX9 expression
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cisplatin • carboplatin
2ms
SOX2 Expression Does Not Guarantee Cancer Stem Cell-like Characteristics in Lung Adenocarcinoma. (PubMed, Cells)
Ultimately, our findings demonstrate that SOX2 is not absolutely essential in LUAD cancer cells. This emphasizes the necessity of considering cancer subtype-dependent and context-dependent factors when targeting SOX2 overexpression as a potential therapeutic vulnerability in diverse cancers.
Journal • Cancer stem
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SOX2
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SOX2 overexpression • SOX2 expression
4ms
SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer. (PubMed, Cell Death Dis)
Additionally, clinical analyses showed that increased levels of AC005392.2, GLUT1, and EPHA2 expression were positively correlated with SOX2 and were also associated with poor prognoses in patients with CRC. Our study conclusively demonstrates that the SOX2-lncRNA AC005392.2-GLUT1 signaling axis regulates VM formation in CRC, offering a foundation for the development of new antiangiogenic drugs or new drug combination regimens.
Journal
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SOX2 • EPHA2 (EPH receptor A2) • SLC2A1 (Solute Carrier Family 2 Member 1)
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SOX2 overexpression • SOX2 expression
5ms
Targeting SOX2 in glioblastoma cells reveals heterogeneity in SOX2 dependency (SNO 2023)
In current work, SOX2-dependent cell lines are engineered to express inducible exogenous SOX2 with concomitant endogenous SOX2 knockout, providing a system where SOX2 can be turned off at any time point. This system will be used in further studies elucidating the nature of SOX2 dependence and independence in GBM stem cells.
SOX2
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SOX2 overexpression • SOX2 expression
5ms
Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma. (PubMed, Nucleic Acids Res)
Notably, we show that the conserved SRR124 and SRR134 regions are essential during mouse development, where homozygous deletion results in the lethal failure of esophageal-tracheal separation. These findings provide insights into how developmental enhancers can be reprogrammed during tumorigenesis and underscore the importance of understanding enhancer dynamics during development and disease.
Journal
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FOXA1 (Forkhead Box A1) • SOX2 • NFIB (Nuclear Factor I B)
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SOX2 overexpression • SOX2 expression
7ms
Tumor-intrinsic Sox2 signaling induces regulatory T cell-mediated CD8 T cell exclusion, promoting resistance to checkpoint blockade therapy in lung cancer (SITC 2023)
Furthermore, we showed that combining a neutralizing antibody against DKK1 with CBT significantly reduced the density of regulatory T cells in the TME, increased CD8 T cell infiltration, and improved tumor control. Conclusions Our results show that tumor cell-intrinsic activation of Sox2 in NSCLC promotes immune evasion and contributes to immunotherapy resistance by retaining effector CD8 T cells outside of the tumor mass.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Checkpoint block
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • SOX2 • FOXP3 (Forkhead Box P3)
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KRAS G12D • KRAS G12 • SOX2 overexpression • SOX2 expression
7ms
Long non-coding RNA SOX21-AS1: A potential tumor oncogene in human cancers. (PubMed, Pathol Res Pract)
SOX21-AS1 was also proved to enhance the resistance of ovarian cancer cells to cisplatin chemotherapy...Overexpression of SOX21-AS1 is related to various cancer-related pathways, like epithelial mesenchymal transition (EMT), invasion, migration, apoptosis, and cell cycle arrest. In this work, we aimed to discuss the biogenesis, function, and underlying molecular mechanism of SOX21-AS1 in cancer progression as well as its potential as a prognostic and diagnostic biomarker in human cancers.
Review • Journal
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TGFB1 (Transforming Growth Factor Beta 1) • YBX1 (Y-Box Binding Protein 1) • SOX21-AS1 (SOX21 Antisense Divergent Transcript 1)
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SOX2 overexpression
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cisplatin
7ms
Overexpression of SOX2 Gene by Histone Modifications: SOX2 Enhances Human Prostate and Breast Cancer Progression by Prevention of Apoptosis and Enhancing Cell Proliferation. (PubMed, Oncology)
Histone modification is crucial for the overexpression of SOX2 during tumor development and cancer progression. These findings show the avenue of co-targeting SOX2 and its active epigenetic modifier enzymes to effectively treat aggressive prostate and breast cancers.
Journal • Epigenetic controller
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SOX2
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SOX2 overexpression • SOX2 expression
9ms
Activin and Hepatocyte Growth Factor Promotes Colorectal Cancer Stemness and Metastasis through FOXM1/SOX2/CXCR4 Signaling. (PubMed, Gut Liver)
Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis. Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.
Journal
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HGF (Hepatocyte growth factor) • SOX2 • FOXM1 (Forkhead Box M1)
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SOX2 overexpression • SOX2 expression
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thiostrepton (RSO-021)
9ms
Molecular Characterization of Esophageal Squamous Cell Carcinoma Using Quantitative Proteomics. (PubMed, Cancers (Basel))
Interestingly, there are also other non-canonical substrates of SYVN1 which are known to play a crucial role in tumor progression. Thus, SYVN1 could be a potential therapeutic target in ESCC.
Journal
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TOP2A (DNA topoisomerase 2-alpha) • MMP2 (Matrix metallopeptidase 2) • SOX2 • TP63 (Tumor protein 63) • IGF2BP2 (Insulin Like Growth Factor 2 MRNA Binding Protein 2) • POSTN (Periostin)
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SOX2 overexpression • SOX2 expression
9ms
Control of SOX2 protein stability and tumorigenic activity by E3 ligase CHIP in esophageal cancer cells. (PubMed, Oncogene)
Taken together, our study has identified CHIP as a key suppressor of SOX2 protein stability and tumorigenic activity and revealed CHIP nuclear exclusion as a potential mechanism for aberrant SOX2 overexpression in esophageal cancer. Our study also suggests HSP90 inhibitors as potential therapeutic agents for SOX2-positive cancers.
Journal • IO biomarker
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SOX2 • XPO1 (Exportin 1)
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SOX2 overexpression • SOX2 expression
9ms
GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma. (PubMed, Oncogene)
Finally, we demonstrated in tumor xenograft model that GSK3β inhibitor AR-A014418 was effective in suppressing SOX2-positive ESCC tumor progression and inhibited tumor progression cooperatively with chemotherapeutic agent carboplatin. In conclusion, we uncovered a novel role for GSK3β in driving SOX2 overexpression and tumorigenesis and provided evidence that targeting GSK3β may hold promise for the treatment of recalcitrant ESCCs.
Journal
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CUL4A (Cullin 4A) • SOX2 • GSK3B (Glycogen Synthase Kinase 3 Beta)
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SOX2 overexpression • SOX2 expression
|
carboplatin
10ms
SOX2 Promotes Radioresistance in Non-small Cell Lung Cancer by Regulating Tumor Cells Dedifferentiation. (PubMed, Int J Med Sci)
Our study revealed that SOX2 regulates radiotherapy resistance in NSCLC via promoting cell dedifferentiation. Therefore, SOX2 may be a promising therapeutic target for overcoming radioresistance in NSCLC, providing a new perspective to improve the curative effect.
Journal • Tumor cell
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SOX2
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SOX2 overexpression • SOX2 expression
12ms
SOX2 downregulation of PML increases HCMV gene expression and growth of glioma cells. (PubMed, PLoS Pathog)
Lastly, the expression of SOX2 and HCMV immediate early 1 (IE1) protein could be correlated in tissues from glioma patients, and interestingly, elevated levels of SOX2 and IE1 were predictive of a worse clinical outcome. These studies argue that HCMV gene expression in gliomas is regulated by SOX2 through its regulation of PML expression and that targeting molecules in this SOX2-PML pathway could identify therapies for glioma treatment.
Journal
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SOX2
|
SOX2 overexpression • SOX2 expression
1year
p21-activated kinase 2 binds to transcription factor SOX2 and up-regulates DEK to promote the progression of lung squamous cell carcinoma. (PubMed, Lab Invest)
Moreover, SOX2 activated the expression of DEK, and silencing DEK attenuated the malignant behaviors of LSCC cells. In conclusion, PAK2 could bind to the transcription factor SOX2 and thus activate the expression of DEK, thereby driving the malignant phenotypes of LSCC cells both in vivo and in vitro.
Journal
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SOX2 • PAK2 (P21 (RAC1) Activated Kinase 2)
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SOX2 overexpression • PAK2 overexpression • SOX2 expression
over1year
SOX2-high cancer cells exhibit an aggressive phenotype, with increases in stemness, proliferation and invasion, as well as higher metabolic activity and ATP production. (PubMed, Aging (Albany NY))
SOX2-high MDA-MB-231 cells also showed a loss of E-cadherin expression, and increased Vimentin expression, consistent with an epithelial-mesenchymal transition (EMT). Therefore, endogenous SOX2 transcriptional activity and protein levels are mechanistically linked to aggressive phenotypic behaviours and energy production in CSCs.
Journal
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CDH1 (Cadherin 1) • SOX2 • VIM (Vimentin)
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CDH1 expression • SOX2 overexpression • VIM expression • SOX2 expression
over1year
Sox2 expression in NSCLC mediates changes in the tumor microenvironment impairing T cell infiltration and promoting resistance to checkpoint blockade therapy (SITC 2022)
Conclusions Our results show that tumor cell-intrinsic activation of Sox2 in NSCLC promotes immune evasion and contributes to immunotherapy resistance by inducing changes in the TME. Understanding the molecular and immunological mechanisms mediating T cell exclusion from the lung TME will facilitate the development of novel combination treatment strategies for NSCLC patients.
Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • SOX2
|
PD-L1 expression • KRAS G12D • KRAS G12 • SOX2 overexpression • SOX2 expression • KRAS expression
over1year
p21-activated kinase 2 binds to transcription factor SOX2 and up-regulates DEK to promote the progression of lung squamous cell carcinoma. (PubMed, Lab Invest)
Moreover, SOX2 activated the expression of DEK, and silencing DEK attenuated the malignant behaviors of LSCC cells. In conclusion, PAK2 could bind to the transcription factor SOX2 and thus activate the expression of DEK, thereby driving the malignant phenotypes of LSCC cells both in vivo and in vitro.
Journal
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SOX2 • PAK2 (P21 (RAC1) Activated Kinase 2)
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SOX2 overexpression • PAK2 overexpression • SOX2 expression
almost2years
Investigation of the RB1-SOX2 axis constitutes a tool for viral status determination and diagnosis in Merkel cell carcinoma. (PubMed, Virchows Arch)
SOX2 diffuse expression was observed in 92% of the MCC cases and almost never observed in non-neuroendocrine skin epithelial neoplasms (2%, p < 0.0001, LHR +  = 59). Furthermore, SOX2 diffuse staining was more frequently observed in MCCs than in extra-cutaneous NECs (30%, p < 0.001, LHR +  = 3.1).These results confirm RB1 as a robust predictor of MCC viral status and further suggest SOX2 to be a relevant diagnostic marker of MCC.
Journal
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RB1 (RB Transcriptional Corepressor 1) • SOX2
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RB1 expression • RB1 positive • SOX2 overexpression • SOX2 expression
2years
SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling. (PubMed, Med Oncol)
Meaningfully, patients with low expression of SOX2, and even including its regulating APE1, survived longer than those with high expression of SOX2, and APE1. siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.
Journal
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SOX2
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SOX2 overexpression
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cisplatin
2years
Understanding the mechanism of neuropilin2 upregulation in advanced prostate cancer (AACR 2022)
We demethylated the NRP2 promoter by treatment with 5’Azacytidine and checked NRP2 mRNA expression... The differential expression of NRP2 in advanced prostate cancer is a two-step process of initial demethylation of the DNA in the NRP2 promoter region, followed by binding of SOX2
Late-breaking abstract
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RB1 (RB Transcriptional Corepressor 1) • SOX2
|
SOX2 overexpression
|
azacitidine
over2years
Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers? (PubMed, Molecules)
Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CD44 (CD44 Molecule) • SOX2 • CASP3 (Caspase 3) • CASP9 (Caspase 9) • MMP9 (Matrix metallopeptidase 9)
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CD44 expression • SOX2 overexpression
over2years
SOX2 and Bcl-2 as a Novel Prognostic Value in Hepatocellular Carcinoma Progression. (PubMed, Curr Oncol)
A significant correlation was observed: patients with SOX2 overexpression had a lower 5-year overall survival rate (p = 0.04); however, there was no significant association between Bcl-2 and survival (p = 0.5). Collectively, overexpression of SOX2 and Bcl-2, alone or combined, may be a potential marker to evaluate prognosis and response to HCC treatment.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • SOX2 • BAX (BCL2-associated X protein)
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BCL2 overexpression • BCL2 expression • BAX expression • SOX2 overexpression
over2years
Design and Characterization of a Cell-Penetrating Peptide Derived from the SOX2 Transcription Factor. (PubMed, Int J Mol Sci)
Predictions of the free energy of binding revealed that the iPep largely retained the binding affinity for DNA of parental SOX2. This work will enable the future engineering of novel dominant interference peptides to transport different therapeutic cargo molecules such as anti-cancer drugs into cells.
Journal
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FGF4 (Fibroblast growth factor 4) • SOX2 • POU5F1 (POU Class 5 Homeobox 1)
|
SOX2 overexpression
over2years
Transcription factor SOX2 contributes to nonalcoholic fatty liver disease development by regulating the expression of the fatty acid transporter CD36. (PubMed, FEBS Lett)
Transcriptional regulation of CD36 by SOX2 suggested the involvement of CD36 in SOX2-mediated hepatic steatosis. Thus, SOX2 may be a target to prevent NAFLD development.
Journal
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CD36 (thrombospondin receptor) • SOX2
|
SOX2 overexpression
over2years
MSX2 represses tumor stem cell phenotypes within oral squamous cell carcinomas via SOX2 degradation. (PubMed, Exp Biol Med (Maywood))
Cells with MSX2 overexpression or knockdown formed smaller or bigger cancers in vivo, thereby showing a lower or a higher tumor incidence, respectively. Thus, our results confirm that MSX2 has a tumor suppression effect on the cancer stem cell phenotypes of OSCC and indicate that the MSX2-SOX2 signaling pathway could be a useful target for OSCC treatment.
Journal
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CD44 (CD44 Molecule) • SOX2 • CD24 (CD24 Molecule)
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CD44 expression • SOX2 overexpression
over2years
LncRNA SOX2-OT/miR-30d-5p/PDK1 Regulates PD-L1 Checkpoint Through the mTOR Signaling Pathway to Promote Non-small Cell Lung Cancer Progression and Immune Escape. (PubMed, Front Genet)
Then, the combined application of overexpressed PDK1 and rapamycin verified that PDK1 could regulate the expression of PD-L1 in NSCLC cells through the mTOR signaling pathway...Finally, tumor formation assay in animals confirmed that overexpression of SOX2-OT could promote the growth of NSCLC tumor in vivo. In this study, assays in vitro and in vivo were conducted to elucidate the mechanism by which SOX2-OT/miR-30d-5p/PDK1 drives PD-L1 through the mTOR signaling pathway to promote the malignant progression and immune escape of NSCLC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • SOX2 • MIR30D (MicroRNA 30d) • PDPK1 (3-Phosphoinositide dependent protein kinase 1)
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PD-L1 expression • SOX2 overexpression
|
sirolimus
over2years
A proteogenomic portrait of lung squamous cell carcinoma. (PubMed, Cell)
Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • BIRC5 (Baculoviral IAP repeat containing 5) • SOX2 • TP63 (Tumor protein 63)
|
FGFR1 amplification • CDKN2A mutation • EZH2 overexpression • SOX2 overexpression
over2years
Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. (PubMed, Nat Genet)
Moreover, oncogenic Sox2 activates endogenous retroviruses, inducing expression of double-stranded RNA and dependence on the RNA editing enzyme ADAR1. These data reveal SOX2 functions in ESCC, defining targetable vulnerabilities.
Journal
|
TP53 (Tumor protein P53) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SOX2 • ADAR (Adenosine Deaminase RNA Specific)
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SOX2 overexpression
over2years
Expression of SOX2 and OCT4 in odontogenic cysts and tumors. (PubMed, Head Face Med)
SOX2 is differentially expressed in odontogenic cysts and tumors. This could be related to their diverse cells of origin or stages of histogenesis. The overexpression of SOX2 and OCT4 in OKC indicates the acquired stem-like property. Future studies should investigate whether the overexpression of OCT4 and SOX2 contributes to the aggressive behaviors of the tumors.
Journal
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SOX2 • POU5F1 (POU Class 5 Homeobox 1)
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SOX2 overexpression • POU5F1 expression
over2years
Anaplastic lymphoma kinase (ALK) overexpression is associated with aggressive phenotypic characteristics of ovarian high-grade serous carcinoma. (PubMed, Am J Pathol)
Finally, ALK overexpression was due to increased expression of neuroendocrine markers including synaptophysin, CD56, and BCL2 in HGCS tissues. These findings suggest that overexpression of full-length ALK may influence the biological behavior of HGSC through cooperation with ELAVL3 and Sox factors, leading to establishment and maintenance of the aggressive phenotypic characteristics of HGSC.
Journal • IO biomarker
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ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • NCAM1 (Neural cell adhesion molecule 1) • SOX2
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SOX2 overexpression
almost3years
The m6A methyltransferase METTL3 promotes the stemness and malignant progression of breast cancer by mediating m6A modification on SOX2. (PubMed, J BUON)
METTL3 is upregulated in BCa, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.
Journal
|
CD44 (CD44 Molecule) • SOX2 • IGF2BP2 (Insulin Like Growth Factor 2 MRNA Binding Protein 2) • METTL3 (Methyltransferase Like 3)
|
SOX2 overexpression
3years
CDK1 promotes the stemness of lung cancer cells through interacting with Sox2. (PubMed, Clin Transl Oncol)
This work reveals a novel CDK1/Sox2 axis responsible for maintaining the stemness of lung cancer cells.
Journal
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SOX2 • POU5F1 (POU Class 5 Homeobox 1) • CDK1 (Cyclin-dependent kinase 1) • NANOG (Nanog Homeobox)
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SOX2 overexpression